Nasal Bacterial Microbiome: Probing a Healthy Porcine Family

Upper respiratory tract (URT) infection caused the leading and devastating diseases in pigs. It was believed that the normal microbiome of URT plays a vital role in health and disease development. As the entry point of the URT, little knowledge of bacterial microbiome in porcine nasal was known. A cultivation-independent approach directly to 16s ribosomal RNA genes enabled us to reveal the nasal bacterial community, structure and diversity. Here, we found that an unprecedented 207 phylotypes were characterized from 933 qualified clones, indicating the variable, species richness but particularly dominant bacterial microbiome. The dominant species were from genus Comamonas and Acinetobacter, which constitute core normal bacterial microbiome in porcine nasal. Moreover, a set of swine specific pathogens and zoonotic agents were detected in the swine nasal microbiome. Collectively, we provided a snapshot of our current knowledge of the community structure of porcine nasal bacterial ecosystem in a healthy family that will further enhance our view to understand URT infection and public health

Sustaining the ecosystem of higher education in China: Perspectives from young researchers

The sustainable development of higher education in China has been a key priority for the national, social, economic and political development. Responding to the severe competition in various university ranking systems, most universities in China have set aims to enhance their sustainability in research and publication. There has been a prominent conflict that young scholars are expected to be productive, with publications in academic journals, competitive in receiving national and municipal research grants, and prestigious in the national and international arenas, or they will be terminated by the ‘six-year-up-or-out’ policy. Recent reform in higher education that calls for a sustainable development for young researchers is a strategy to revert the side effects from global university ranking systems by nurturing young researchers in their early academic lives, enhancing their productivity in research and publication internationally, and enhancing their global competitiveness without harming sustainability in academic development. This research explored (i) the difficulties that most young scholars face in sustainable academic research development, (ii) the factors that enhance or inhibit research productivity of young researchers, and (iii) the work lives in their early-career development in China. A qualitative study was conducted with data obtained from semistructured, in-depth interviews of 24 young university researchers from three provinces and a municipality in China. Findings show that factors that relate to sustainable research productivity are individual attributes, discipline attributes, institutional attributes and policy attributes. Lastly, suggestions for policy making in higher education and for improving sustainable research development of young researchers in China are provided and implications for future research are discussed

Planning and coordinated response mechanism of economic and ecological services in urban expansion

Against the backdrop of urban sustainable development around the world, how to coordinate both economic growth and ecological benefits in urban space becomes an important problem. Therefore, this study simulated and predicted the spatiotemporal changes in urban economy and ecosystem service value (E.S.V.) equivalent ratio under the current policies by 2030, and analysed how adjusting planning policies influences economy and ecology. This process was based on the future land use simulation (F.L.U.S.) model of coupled neural network, and on methods assessing the spatial changes in ecosystem services and land economy. This study aims to analyse urban land economy and E.S.V., and assess how China’s land spatial planning guides and promotes high-quality urban economic development. Results show that artificial intelligence (A.I.) simulation can forecast the results of spatial planning policies of national lands, to make policy-making more forwardlooking. The guidance of planning policies on urban expansion accelerates the increase in economic value of urban residential and commercial lands, thereby promoting the economic growth. However, adjusted planning policies may lead to ecological destruction. So, this study provides model verifications and path guidance to realise coordinated sustainable development between economy and ecology, serving as an important reference to formulating proper policies for urban development

Seneca Valley Virus 2C and 3Cpro Induce Apoptosis via Mitochondrion-Mediated Intrinsic Pathway

Seneca Valley virus (SVV) is the only member of the genus Senecavirus of the Picornaviridae family. SVV can selectively infect and lyse tumor cells with neuroendocrine features and is used as an oncolytic virus for treating small-cell lung cancers. However, the detailed mechanism underlying SVV-mediated destruction of tumor cells remains unclear. In this study, we found that SVV can increase the proportion of apoptotic 293T cells in a dose- and time-dependent manner. SVV-induced apoptosis was initiated via extrinsic and intrinsic pathways through activation of caspase-3, the activity of which could be attenuated by a pan-caspase inhibitor (Z-VAD-FMK). We confirmed that SVV 2C and 3Cpro play critical roles in SVV-induced apoptosis. The SVV 2C protein was located solely in the mitochondria and activated caspase-3 to induce apoptosis. SVV 3Cpro induced apoptosis through its protease activity, which was accompanied by release of cytochrome C into the cytoplasm, but did not directly cleave PARP1

African swine fever virus pA104R protein acts as a suppressor of type I interferon signaling

This study evaluates the role of the late viral protein, pA104R, in African swine fever virus immunosuppression. ASFV-encoded pA104R is a putative histone-like protein that is highly conserved throughout different virulent and non-virulent isolates. Previous studies have demonstrated that pA104R plays a vital role in the ASFV replication cycle and is a potential target for antiviral therapy. Here, we demonstrated that pA104R is a potent antagonist of type I interferon signaling. IFN-stimulated response element activity and subsequent transcription of co-transfected and endogenous interferon-stimulated genes were attenuated by pA104R treatment in HEK-293 T cells. Immunoprecipitation assay and reciprocal pull-down showed that pA104R does not interact directly with STAT1, STAT2, or IRF9. However, pA104R could inhibit IFN signaling by attenuating STAT1 phosphorylation, and we identified the critical amino acid residues (R/H69,72 and K/R92,94,97) involved through the targeted mutation functional assays. Although pA104R is a histone-like protein localized to the nucleus, it did not inhibit IFN signaling through its DNA-binding capacity. In addition, activation of the ISRE promoter by IRF9-Stat2(TA), a STAT1-independent pathway, was inhibited by pA104R. Further results revealed that both the transcriptional activation and recruitment of transcriptional stimulators by interferon-stimulated gene factor 3 were not impaired. Although we failed to determine a mechanism for pA104R-mediated IFN signaling inhibition other than attenuating the phosphorylation of STAT1, these results might imply a possible involvement of epigenetic modification by ASFV pA104R. Taken together, these findings support that pA104R is an antagonist of type I interferon signaling, which may interfere with multiple signaling pathways

Circulating microRNA-92a and microRNA-21 as novel minimally invasive biomarkers for primary breast cancer

PURPOSE: MicroRNAs (miRNAs) play an essential role in breast malignant tumor development and progression. The development of clinically validated biomarkers for primary breast cancer (BC) has remained an insurmountable task despite other advances in the field of cancer molecular biology. The objective of this study is to investigate the differential expression of miRNAs and the potential of circulating microRNAs as novel primary breast cancer biomarkers. METHODS: Our analyses were performed on 48 tissue and 100 serum samples of patients with primary BC and a set of 20 control samples of healthy women, respectively. The relative expression of ten candidate miRNAs (miR-106b, miR-125b, miR-17, miR-185, miR-21, miR-558, miR-625, miR-665, miR-92a, and miR-93) from the results of four bioinformatics approaches and literature curation was measured by real-time quantitative reverse transcription PCR (qRT-PCR). RESULTS: The level of miR-92a was significantly lower, while miR-21 was higher, as previous reports, in tissue and serum samples of BC than that of healthy controls (p < 0.001). Logistic regression and receiver operating characteristic curve analyses revealed the significant and independent value (p < 0.001) of the miR-92a and miR-21 expression quantification in serums. Moreover, the comparison with the clinicopathologic data of the BC patients showed that decreased levels of miR-92a and increased levels of miR-21 were associated with tumor size and a positive lymph node status (p < 0.001). CONCLUSIONS: These findings suggest that many miRNAs expressions are altered in BC, whose expression profiling may provide a useful clue for the pathophysiological research. Circulating miR-92a has potential use as novel breast cancer biomarker, which is comparable to miR-21

Japanese Encephalitis Virus wild strain infection suppresses dendritic cells maturation and function, and causes the expansion of regulatory T cells

<p>Abstract</p> <p>Background</p> <p>Japanese encephalitis (JE) caused by Japanese encephalitis virus (JEV) accounts for acute illness and death. However, few studies have been conducted to unveil the potential pathogenesis mechanism of JEV. Dendritic cells (DCs) are the most prominent antigen-presenting cells (APCs) which induce dual humoral and cellular responses. Thus, the investigation of the interaction between JEV and DCs may be helpful for resolving the mechanism of viral escape from immune surveillance and JE pathogenesis.</p> <p>Results</p> <p>We examined the alterations of phenotype and function of DCs including bone marrow-derived DCs (bmDCs) <it>in vitro </it>and spleen-derived DCs (spDCs) <it>in vivo </it>due to JEV P3 wild strain infection. Our results showed that JEV P3 infected DCs <it>in vitro </it>and <it>in vivo</it>. The viral infection inhibited the expression of cell maturation surface markers (CD40, CD80 and CD83) and MHCⅠ, and impaired the ability of P3-infected DCs for activating allogeneic naïve T cells. In addition, P3 infection suppressed the expression of interferon (IFN)-α and tumor necrosis factor (TNF)-α but enhanced the production of chemokine (C-C motif) ligand 2 (CCL2) and interleukin (IL)-10 of DCs. The infected DCs expanded the population of CD4+ Foxp3+ regulatory T cell (Treg).</p> <p>Conclusion</p> <p>JEV P3 infection of DCs impaired cell maturation and T cell activation, modulated cytokine productions and expanded regulatory T cells, suggesting a possible mechanism of JE development.</p

Japanese encephalitis virus infection induces changes of mRNA profile of mouse spleen and brain

<p>Abstract</p> <p>Background</p> <p>Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus, leading to an acute encephalitis and damage to the central nervous system (CNS). The mechanism of JEV pathogenesis is still unclear. DNA microarray analyses have been recently employed to detect changes in host gene expression, which is helpful to reveal molecular pathways that govern viral pathogenesis. In order to globally identify candidate host genes associated with JEV pathogenesis, a systematic mRNA profiling was performed in spleens and brains of JEV-infected mice.</p> <p>Results</p> <p>The results of microarray analysis showed that 437 genes in spleen and 1119 genes in brain were differentially expressed in response to JEV infection, with obviously upregulated genes like pro-inflammatory chemokines and cytokines, apoptosis-related proteases and IFN inducible transcription factors. And the significant pathways of differentially expressed genes are involved in cytokine-cytokine receptor interaction, natural killer cell mediated cytotoxicity, antigen processing and presentation, MAPK signaling, and toll-like receptor signaling, etc. The differential expression of these genes suggests a strong antiviral response of host but may also contribute to the pathogenesis of JEV resulting in encephalitis. Quantitative RT-PCR (RT-qPCR) assay of some selected genes further confirmed the results of microarray assay.</p> <p>Conclusions</p> <p>Data obtained from mRNA microarray suggests that JEV infection causes significant changes of mRNA expression profiles in mouse spleen and brain. Most of differentially expression genes are associated with antiviral response of host, which may provide important information for investigation of JEV pathogenesis and therapeutic method.</p